Objective: To understand specific molecular features of Parkinson’s disease associated with mutations in the GBA gene (GBA-PD), we analyzed the gene expression profile of peripheral-blood monocyte-derived (PBMD)-macrophages from GBA-PD patients, asymptomatic GBA mutations carriers (GBA-Carriers) and Controls and its enriched pathways.
Background: Mutations in the GBA gene are the greatest genetic risk factor for Parkinson’s disease (PD). Not every carrier of GBA mutations will develop PD during lifetime.
Method: Sequencing of total RNA isolated using TRIzol (Invitrogen, USA) from PBMD-macrophages of 5 GBA-PD patients, 4 GBA-Carriers, 4 Controls was conducted using HiSeq1500 (Illumina, USA), generating at least 15 million 50-base-long reads per library. After alignment on GRCH38 genome, differentially expressed genes (DEGs) were obtained between each pair of groups. DEGs were selected based on a fold change (FC) threshold (FC>1.5) and an FDR-corrected p of a moderated Wald test <0.05, as assessed using DESeq2 R package. DEGs that were significantly differentially expressed between groups were selected for gene set enrichment analysis (GSEA) in R.
Results: 28 differentially expressed genes were identified in GBA-PD patients compared to controls, 8 differentially expressed genes were revealed in GBA-Carriers and controls and 23 differentially expressed genes were found in GBA-PD patients and GBA-Carriers. These genes were included in processes associated with inflammatory response, autophagy, mitochondrial networks, cell signaling, according to the results of an enrichment analysis.
Conclusion: Overlapping of DEGs determined by Venn diagram between groups revealed two differentially expressed genes (HOOK2, JUNB) in GBA-PD patients and GBA-Carriers compared to Controls therefore we assume that alteration of their expression is characterized for all GBA mutations carriers; two differentially expressed genes (IL31RA, ACOD1) in GBA-Carriers compared to GBA-PD and Controls that can be considered as potential genetic protective factors for PD development in GBA mutation carriers and 7 differentially expressed genes (COLEC12, RPL18, ARL4C, TPTEP1, TRIM13, BCL6, DUSP1) in GBA-PD patients compared to GBA-Carriers and Controls that can be considered as potential triggers for PD among GBA mutations carriers. The study was supported by the Russian Science Foundation grant N19-15-00315.
To cite this abstract in AMA style:
T. Usenko, A. Panteleeva, K. Basharova, M. Nikolaev, A. Kopytova, A. Bezrukova, K. Senkevich, I. Miliukhina, E. Zakharova, S. Pchelina. Whole-transcriptome analysis of monocyte-derived macrophages from patients with Parkinson’s disease associated with mutations in the GBA gene [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/whole-transcriptome-analysis-of-monocyte-derived-macrophages-from-patients-with-parkinsons-disease-associated-with-mutations-in-the-gba-gene/. Accessed May 21, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/whole-transcriptome-analysis-of-monocyte-derived-macrophages-from-patients-with-parkinsons-disease-associated-with-mutations-in-the-gba-gene/